Fragmentation of Care in Patients with Peritoneal Metastases Undergoing Cytoreductive Surgery.

BACKGROUND: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes. PATIENTS AND METHODS: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups. RESULTS: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar. CONCLUSIONS: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. METHODS: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively. RESULTS: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98). CONCLUSIONS: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Regulation of integrin and extracellular matrix genes by HNRNPL is necessary for epidermal renewal.

Stratified epithelia such as the epidermis require coordinated regulation of stem and progenitor cell proliferation, survival, and differentiation to maintain homeostasis. Integrin-mediated anchorage of the basal layer stem cells of the epidermis to the underlying dermis through extracellular matrix (ECM) proteins is crucial for this process. It is currently unknown how the expression of these integrins and ECM genes are regulated. Here, we show that the RNA-binding protein (RBP) heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to these genes on chromatin to promote their expression. HNRNPL recruits RNA polymerase II (Pol II) to integrin/ECM genes and is required for stabilizing Pol II transcription through those genes. In the absence of HNRNPL, the basal layer of the epidermis where the stem cells reside prematurely differentiates and detaches from the underlying dermis due to diminished integrin/ECM expression. Our results demonstrate a critical role for RBPs on chromatin to maintain stem and progenitor cell fate by dictating the expression of specific classes of genes.

Intubation and In-Hospital Mortality After Trauma With Glasgow Coma Scale Score Eight or Less-A Cohort Study.

INTRODUCTION: Most trauma societies recommend intubating trauma patients with Glasgow Coma Scale (GCS) scores ≤8 without robust supporting evidence. We examined the association between intubation and 30-d in-hospital mortality in trauma patients arriving with a GCS score ≤8 in an Indian trauma registry. METHODS: Outcomes of patients with a GCS score ≤8 who were intubated within 1 h of arrival (intubation group) were compared with those who were intubated later or not at all (nonintubation group) using various analytical approaches. The association was assessed in various subgroup and sensitivity analyses to identify any variability of the effect. RESULTS: Of 3476 patients who arrived with a GCS score ≤8, 1671 (48.1%) were intubated within 1 h. Overall, 1957 (56.3%) patients died, 947 (56.7%) in the intubation group and 1010 (56.0%) in the nonintubation group, with no significant difference in mortality (odds ratio = 1.2 [confidence interval, 0.8-1.8], P value = 0.467) in multivariable regression and propensity score-matched analysis. This result persisted across subgroup and sensitivity analyses. Patients intubated within an hour of arrival had longer durations of ventilation, intensive care unit stay, and hospital stay (P < 0.001). CONCLUSIONS: Intubation within an hour of arrival with a GCS score ≤8 after major trauma was not associated with differences in-hospital mortality. The indications and benefits of early intubation in these severely injured patients should be revisited to promote optimal resource utilization in LMICs.

Design and Implementation of a Learner-Centered Self-Paced Peritoneal Oncology Education Program.

BACKGROUND: Current educational programs for peritoneal surface malignancies (PSM) are unstructured and often target advanced learners. The authors describe the design and implementation of a structured, self-paced course at a high-volume PSM center. METHODS: In 2020, a learner-centered course was designed using the Canvas educational platform in consultation with the Center for Teaching at the University of Chicago. The course consisted of disease-site-specific modules, perioperative care pathways, in-built voluntary quizzes, and multimedia supplements for advanced learners. Trainees were provided access during the PSM service rotation, and engagement was compared across training levels by measuring the time spent online. RESULTS: Course design and management required 71 h between 2020 and 2022, with the majority of time spent in the design phase. During 3 years, 62 personnel (21 [34%] medical students, 28 [45%] residents, 8 [13%] staff, and 5 [8%] fellows) were assigned the course. The overall engagement rate was 83.9% (86% of medical students, 75% of residents, 100% of staff and fellows), and the median time spent online was 12.4 min/week (interquartile range [IQR], 2.1-53.0 min/week). Fourth-year medical students and clinical fellows spent more time online than other learners (73 min/week [IQR, 24.5-100 min/week] vs 13.3 min/week [IQR, 7.3-26.5 min/week]) (p = 0.001). CONCLUSIONS: The design and implementation of a PSM-specific course was feasible and sustainable using an online learning platform. Higher engagement was noted among invested learners. Non-technical factors for reduced engagement need to be ascertained further to improve the next iteration of this course.

A Case Series of Nephrotic Syndrome: A Harbinger of Catastrophic Oncologic Diseases.

INTRODUCTION: A cancer patient can have numerous complications involving the kidneys, ranging from acute kidney injury, chronic kidney disease, glomerulopathies, electrolyte, and acid-base disorders. It can be due to the malignancy itself or due to chemotherapeutic agents. Paraneoplastic glomerulopathy is a rare presentation of neoplastic disease. CASE DISCUSSION: We present a case series of two patients presenting with nephrotic syndrome as a paraneoplastic syndrome associated with a gynecologic tumor. Both patients responded only partially to steroids and immunosuppressive therapy. Complete remission was only achieved after treatment of primary malignancy. CONCLUSION: It is critical to recognize this entity as immunosuppression may induce a flare in the tumor course and worsen outcomes. So, age-appropriate screening of malignancy should ideally be performed in any adult patient with nephrotic syndrome.

Mortality and Risk Factors in Isolated Traumatic Brain Injury Patients: A Prospective Cohort Study.

INTRODUCTION: Outcomes in patients with isolated traumatic brain injury (iTBI) have not been evaluated comprehensively in low-income and middle-income countries. We aimed to study the in-hospital iTBI mortality and its associated risk factors in a prospective multicenter Indian trauma registry. METHODS: Patients with iTBI (head and neck Abbreviated Injury Score ≥2 and other region Abbreviated Injury Score ≤2) were included. Study variables comprised age, gender, mechanism of injury, systolic blood pressure (SBP) at arrival, Glasgow Coma Scale (GCS) score - classified as mild (13-15), moderate (9-12), and severe (3-8), transfer status, and time to presentation at any participating hospital. A multivariable logistic regression was performed to assess the impact of these factors on 24-h and 30-d mortality following iTBI. RESULTS: Among 5042 included patients, 24-h and 30-d in-hospital mortalities were 5.9% and 22.4%. On a regression analysis, 30-d mortality was associated with age ≥45 y (odds ratio [OR] = 2.1 [1.6-2.7]), railway injury mechanisms (OR = 2.1 [1.3-3.5]), SBP <90 mmHg (OR = 2.6 [1.6-4.1]), and moderate (OR = 3.8 [3.0-5.0]) to severe (OR = 21.1 [16.8-26.7]) iTBI based on GCS scores. 24-h mortality showed similar trends. Patients transferred to the participating hospitals from other centers had higher odds of 30-d mortality (OR = 1.4 [1.2-1.8]) compared to those arriving directly. Those who received neurosurgical intervention had lower odds of 24-h mortality (0.3 [0.2-0.4]). CONCLUSIONS: Age ≥45 y, GCS score ≤12, and SBP <90 mmHg at arrival increased the risk of in-hospital mortality from iTBI.

A Rare Cause of Breathlessness in a Patient on Hemodialysis.

Patients suffering from end stage renal disease (ESRD) often present to the emergency with breathlessness, mostly due to fluid overload. We report a rare case of recurrent unilateral massive pleural effusion in an ESRD patient on maintenance hemodialysis (MHD). The patient was on MHD thrice weekly for the last 2 years with right internal jugular vein (IJV) tunneled cuffed catheter (TCC). Chylothorax was identified as the cause of recurrent pleural effusion which was due to superior vena cava stenosis (SVCO). It was managed successfully by balloon venoplasty of SVC and anticoagulation. SVCO is a rare but a serious complication in patients on long term indwelling dialysis catheters. Physicians involved in the care of dialysis patients must be aware about complications of long term dialysis catheters like central vein stenosis. A strong suspicion of chylothorax should be reserved for a patient with recurrent unilateral pleural effusion and long term dialysis catheters.

Genome-wide analysis of regulatory G-quadruplexes affecting gene expression in human cytomegalovirus.

G-quadruplex (G4), formed by repetitive guanosine-rich sequences, is known to play various key regulatory roles in cells. Herpesviruses containing a large double-stranded DNA genome show relatively higher density of G4-forming sequences in their genomes compared to human and mouse. However, it remains poorly understood whether all of these sequences form G4 and how they play a role in the virus life cycle. In this study, we performed genome-wide analyses of G4s present in the putative promoter or gene regulatory regions of a 235-kb human cytomegalovirus (HCMV) genome and investigated their roles in viral gene expression. We evaluated 36 putative G4-forming sequences associated with 20 genes for their ability to form G4 and for the stability of G4s in the presence or absence of G4-stabilizing ligands, by circular dichroism and melting temperature analyses. Most identified sequences formed a stable G4; 28 sequences formed parallel G4s, one formed an antiparallel G4, and four showed mixed conformations. However, when we assessed the effect of G4 on viral promoters by cloning the 20 putative viral promoter regions containing 36 G4-forming sequences into the luciferase reporter and monitoring the expression of luciferase reporter gene in the presence of G4-stabilizing chemicals, we found that only 9 genes were affected by G4 formation. These results revealed promoter context-dependent gene suppression by G4 formation. Mutational analysis of two potential regulatory G4s also demonstrated gene suppression by the sequence-specific G4 formation. Furthermore, the analysis of a mutant virus incapable of G4 formation in the UL35 promoter confirmed promoter regulation by G4 in the context of virus infection. Our analyses provide a platform for assessing G4 functions at the genomic level and demonstrate the properties of the HCMV G4s and their regulatory roles in viral gene expression.

Chemical-induced formation of BZ-junction with base extrusion.

The crystal structure of BZ-junction reveals that left-handed Z-DNA stabilized by Z-DNA binding domain (Zα) is continuously stacked to right-handed B-DNA with AT bases' extrusion in the junction site. However, this structure might not fully represent the BZ-junction in solution due to the possibility of the junction formation either by crystal packing or Zα interaction. Therefore, we investigated BZ-junction in solution with chemical Z-DNA inducers using CD and 2-aminopurine base-extrusion assay. We confirmed the formation of Z-DNA and BZ-junction with base-extrusion by chemical Z-DNA inducers. However, neither typical Z-DNA nor base-extrusion could be detected with some inducers such as spermine, suggesting that the energy barrier for the formation of the BZ junction might vary depending on the Z-DNA induction conditions.

Total arterial revascularization using robot assisted minimally invasive coronary artery bypass: an Indian experience.

Objective: The aim of this study is to analyze the early outcomes of Total Arterial Revascularization using Robot Assisted Minimally Invasive Coronary Artery Bypass at our center between June 2019 and January 2023. Methods: This is a retrospective analysis of 195 patients who underwent Total Arterial Coronary Revascularization through Robot Assisted Minimally Invasive Coronary Artery Bypass procedure (RA-CABG) during the period of June 2019 and January 2023 in a quaternary care center in India. Primary outcome variables were in-hospital and 30-day mortality. Secondary outcome variables included duration of surgery, length of intensive care unit (ICU) stay, in-hospital stay and perioperative morbidity. The entire patient population was divided into two groups for a subgroup analysis based on when the surgery was conducted i.e. the years since the robotic program was begun at our institution with 81 patients in group I (2019-2021), and 114 patients in group II (2022-2023). Results: 195 patients [88.7% male, mean age of 61.34 ± 9.58 years] underwent RA-CABG during the 5-year period (2019-2023) by a single experienced surgeon and his team. Conversion to larger thoracic incisions was required in 5 cases (2.59%). In-hospital and 30-day mortality was 1.02% each. The average length of ICU stay and hospital stay were 2.82 ± 1.17 days and 5.84 ± 1.71 days respectively. The duration of ICU stay correlated with the number of internal mammary artery grafts procured (p = 0.0022). Median duration of follow-up was 11 months. Overall mortality was 3.62% and cardiac related mortality was 2.07%, and 5 patients (2.59%) underwent percutaneous coronary intervention. Results of the sub-group analysis revealed a statistically significant difference between the groups in terms of number of internal mammary artery grafts procured (p = 0.010), need for transfusions (p = 0.00031), ICU stay (p = 0.0005) and in-hospital stay (p = 0.0006). Conclusions: Total Arterial Coronary Revascularization through RA-CABG is a viable procedure in select patients. An experienced surgeon and team are required. Further studies in the form of randomized trials with long term follow-up are required to establish the overall utility, effectiveness and benefits to the patients.

Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.

BACKGROUND: Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection. STUDY DESIGN: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). RESULTS: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004). CONCLUSIONS: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

Multi-Institutional Study Evaluating the Role of Circulating Tumor DNA in the Management of Appendiceal Cancers.

PURPOSE: Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC. METHODS: Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated. RESULTS: In this cohort of 94 patients with AC, most had grade 2-3 tumors (84.0%) and PM (84.0%). Fifty patients completed the assay in the presence of identifiable disease, among which ctDNA was detected in 4 of 7 (57.1%), 10 of 16 (62.5%), and 19 of 27 (70.4%) patients with grade 1, 2, and 3 diseases, respectively. Patients who had recently received systemic chemotherapy had ctDNA detected less frequently (7 of 16 [43.8%] v 26 of 34 [76.5%]; odds ratio, 0.22 [95% CI, 0.06 to 0.82]; P = .02). Among 36 patients with complete CRS for grade 2-3 AC-PM, 16 (44.4%) developed recurrence (median follow-up, 19.6 months). ctDNA detection was associated with shorter recurrence-free survival (median 11.3 months v not reached; hazard ratio, 14.1 [95% CI, 1.7 to 113.8]; P = .01) and showed high accuracy for the detection of recurrence (sensitivity 93.8%, specificity 85.0%). ctDNA was more sensitive than carcinoembryonic antigen (62.5%), CA19-9 (25.0%), and CA125 (18.8%) and was the only elevated biomarker in four (25%) patients with recurrence. CONCLUSION: This study revealed a reduced ctDNA detection frequency after systemic therapy and accurate recurrence assessment after CRS. These findings underscore the role of ctDNA as a predictive and prognostic biomarker for grade 2-3 AC-PM management.

Early Integrated Palliative Care Within a Surgical Oncology Clinic.

Importance: Advance directive (AD) designation is an important component of advance care planning (ACP) that helps align care with patient goals. However, it is underutilized in high-risk surgical patients with cancer, and multiple barriers contribute to the low AD designation rates in this population. Objective: To assess the association of early palliative care integration with changes in AD designation among patients with cancer who underwent surgery. Design, Setting, and Participants: This cohort study was a retrospective analysis of a prospectively maintained registry of adult patients who underwent elective surgery for advanced abdominal and soft tissue malignant tumors at a surgical oncology clinic in a comprehensive cancer center with expertise in regional therapeutics between June 2016 and May 2022, with a median (IQR) postoperative follow-up duration of 27 (15-43) months. Data analysis was conducted from December 2022 to April 2023. Exposure: Integration of ACP recommendations and early palliative care consultations into the surgical workflow in 2020 using electronic health records (EHR), preoperative checklists, and resident education. Main Outcomes and Measures: The primary outcomes were AD designation and documentation. Multivariable logistic regression was performed to assess factors associated with AD designation and documentation. Results: Among the 326 patients (median [IQR] age 59 [51-67] years; 189 female patients [58.0%]; 243 non-Hispanic White patients [77.9%]) who underwent surgery, 254 patients (77.9%) designated ADs. The designation rate increased from 72.0% (131 of 182 patients) before workflow integration to 85.4% (123 of 144 patients) after workflow integration in 2020 (P = .004). The AD documentation rate did not increase significantly after workflow integration in 2020 (48.9% [89 of 182] ADs documented vs 56.3% [81 of 144] ADs documented; P = .19). AD designation was associated with palliative care consultation (odds ratio [OR], 41.48; 95% CI, 9.59-179.43; P < .001), palliative-intent treatment (OR, 5.12; 95% CI, 1.32-19.89; P = .02), highest age quartile (OR, 3.79; 95% CI, 1.32-10.89; P = .01), and workflow integration (OR, 2.05; 95% CI, 1.01-4.18; P = .048). Patients who self-identified as a race or ethnicity other than non-Hispanic White were less likely to have designated ADs (OR, 0.36; 95% CI, 0.17-0.76; P = .008). AD documentation was associated with palliative care consulation (OR, 4.17; 95% CI, 2.57- 6.77; P < .001) and the highest age quartile (OR, 2.41; 95% CI, 1.21-4.79; P = .01). Conclusions and Relevance: An integrated ACP initiative was associated with increased AD designation rates among patients with advanced cancer who underwent surgery. These findings demonstrate the feasibility and importance of modifying clinical pathways, integrating EHR-based interventions, and cohabiting palliative care physicians in the surgical workflow for patients with advanced care.

Artificial intelligence in gastrointestinal and hepatic imaging: past, present and future scopes.

The use of technology in medicine has grown exponentially because of the technological advancements allowing the digitization of medical data and optimization of their processing to extract multiple features of significant clinical relevance. Radiology has benefited substantially from technical developments and innovations, such as artificial intelligence (AI). This article describes the subsets of AI methods relevant to gastrointestinal and hepatic imaging with examples. We also discuss the evolution of AI, the current challenges, and prospects for further development in the field.

Primary ectopic breast carcinoma arising in the inguinal region in a male patient.

Carcinoma arising in ectopic breast tissue is a rare entity, especially in males, in whom the diagnosis is often delayed due to a low index of suspicion. Conventional imaging techniques fail to characterize the tumor, adding further to the diagnostic dilemma. We report the first case in our knowledge of an extramammary primary breast carcinoma arising in the inguinal region in a male. Our patient, a 69-year-old male, presented with a swelling in the left inguinal region, which was excised and diagnosed as luminal A type invasive ductal carcinoma. He received adjuvant external beam radiotherapy (50 Gy administered in 25 fractions) and tamoxifen. A follow-up examination performed 6 months after the completion of the last dose of radiotherapy showed no residual disease. The modalities of treatment for such tumors have been discussed, with emphasis on surgery and radiotherapy, given the aggressive nature of the disease.

The State of Global Trauma and Acute Care Surgery/Surgical Critical Care.

Trauma is a leading cause of morbidity and mortality globally, with a significant burden attributable to the low- and middle-income countries (LMICs), where more than 90% of injury-related deaths occur. Road injuries contribute largely to the economic burden from trauma and are prevalent among adolescents and young adults. Trauma systems vary widely across the world in their capacity of providing basic and critical care to injured patients, with delays in treatment being present at multiple levels at LMICs. Strengthening existing systems by providing cost-effective and efficient solutions can help mitigate the injury burden in LMICs.